Antibiotic use after a typhoid conjugate vaccine: factors beyond vaccination in low-income countries
Authors: Tapfumanei Mashe, Mateusz Hasso-Agopsowicz, Blessmore V Chaibva
Journal: The Lancet Global Health (2023)

Vaccines have been shown to reduce antimicrobial resistance by reducing the number of drug-sensitive and drug-resistant infections, reducing the use of antibiotics, and reducing the chances of evolution and transmission of resistant genes.1Micoli F Bagnoli F Rappuoli R Serruto D The role of vaccines in combatting antimicrobial resistance.Nat Rev Microbiol. 2021; 19: 287-302Crossref PubMed Scopus (158) Google Scholar, 2Frost I Sati H Garcia-Vello P et al.The role of bacterial vaccines in the fight against antimicrobial resistance: an analysis of the preclinical and clinical development pipeline.Lancet Microbe. 2023; 4: e113-e125Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar A meta-analysis3Buckley BS Henschke N Bergman H et al.Impact of vaccination on antibiotic usage: a systematic review and meta-analysis.Clin Microbiol Infect. 2019; 25: 1213-1225Summary Full Text Full Text PDF PubMed Scopus (60) Google Scholar has shown that there is moderate to high certainty evidence for influenza and pneumococcal conjugate vaccines (PCV) to reduce antibiotic use. Observational studies have found a reduction in antibiotic-resistance rates following the introduction of PCV4Andrejko K Ratnasiri B Hausdorff WP Laxminarayan R Lewnard JA Antimicrobial resistance in paediatric Streptococcus pneumoniae isolates amid global implementation of pneumococcal conjugate vaccines: a systematic review and meta-regression analysis.Lancet Microbe. 2021; 2: e450-e460Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar and modelling studies have highlighted the potential further effect of vaccines in reducing deaths and disability-adjusted life-years associated with resistant pathogens.5Kim C Holm M Frost I Hasso-Agopsowicz M Abbas K Global and regional burden of attributable and associated bacterial antimicrobial resistance avertable by vaccination: modelling study.BMJ Glob Health. 2023; 8e011341Crossref Scopus (1) Google Scholar The typhoid conjugate vaccine (TCV) has had significant effectiveness against drug-sensitive and drug-resistant Salmonella enterica serotype Typhi6Yousafzai MT Karim S Qureshi S et al.Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan: a cohort study.Lancet Glob Health. 2021; 9: e1154-e1162Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar and a modelling analysis has estimated a significant effect on the number of resistant typhoid infections.7Birger R Antillón M Bilcke J et al.Estimating the effect of vaccination on antimicrobial-resistant typhoid fever in 73 countries supported by Gavi: a mathematical modelling study.Lancet Infect Dis. 2022; 22: 679-691Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar In this issue of The Lancet Global Health, Olaru and colleagues8Olaru ID Chingono RMS Bottomley C et al.The effect of a comprehensive typhoid conjugate vaccine campaign on antimicrobial prescribing in children in Harare, Zimbabwe: a mixed methods study.Lancet Glob Health. 2023; 11: 1422-1431Summary Full Text Full Text PDF Scopus (1) Google Scholar found no evidence of an effect on overall antibiotic prescribing rate against typhoid fever 1 year after a Typbar-TCV campaign in Harare, Zimbabwe. However, a trend indicating a reduction in the rate of typhoid antibiotic prescription was observed after the campaign. Importantly, the authors used time series analyses of ecological data which are useful in showing the strong effects of an intervention. As such, the results of this analysis should be interpreted with caution as no evidence for an effect rather than evidence for no effect. We would like to draw attention to three factors not highlighted in the Article that might have contributed to the negative result. First, the absence of change in clinical management of typhoid fever in the study setting could have contributed to the low effect on antibiotic prescribing. If the clinical guidelines and protocols for managing typhoid fever remained unchanged, clinicians might have continued their usual prescribing practices despite the introduction of the vaccine. Second, without a comprehensive and sustained routine immunisation programme, the introduction of a vaccine through a campaign might not have had a significant long-term effect on clinicians' prescribing habits. Establishing routine immunisation protocols and integrating the vaccine into the regular immunisation schedule would provide a more consistent approach to prevention and potentially lead to changes in antibiotic prescribing practices over time. Finally, another factor is the limited scope of the vaccination campaign, which was confined to Harare only. In a setting where individuals travelled from areas outside the city to seek health-care services, including those with symptoms related to typhoid fever, clinicians could not know or predict the child's vaccination status. The uncertainty surrounding the individuals' exposure and immunisation history might have resulted in a preference for prescribing antibiotics. Low-income countries like Zimbabwe have numerous challenges in diagnosing, accessing, and managing infections like typhoid fever. Syndromic management in a stressful environment affects typhoid fever diagnosis and antibiotic prescribing rates. The importance of a conducive environment for optimal antibiotic use is often overlooked. This study emphasises the need to account for various factors beyond vaccination to achieve appropriate antibiotic prescribing as revealed by the rich ethnographic data collected over 8 months. Vaccination should be part of a range of interventions, including proper diagnostics, socioeconomic support, and improving work environments, to enhance patient care and confidence in the quality of care. Primary health-care providers consider societal expectations when making treatment decisions as they are well respected in the society they serve. Compassionate antibiotic prescribing might occur, despite awareness of what would be ideal, due to socioeconomic considerations. Strategies for managing infectious conditions differ across societies, and primary health care is unique due to clinicians' personal connections to the community. Prescribing decisions are influenced by non-clinical factors, such as societal pressures to help their own community, even when it goes against recommendations. Societal challenges (eg, poverty, having personal relationships in the community, and social media) and supply chain issues further affect prescribing behavior. To address these challenges, a comprehensive approach is needed, considering diagnostics, socioeconomic factors, work environments, and access to quality health care. Understanding societal influences and the dynamics of primary health care is crucial for effective case management and antimicrobial stewardship in low-income countries. In conclusion, although vaccines have shown potential in reducing antimicrobial resistance, the study on Typbar-TCV in Harare did not find evidence of an effect on antibiotic prescribing. Factors such as unchanged clinical management, insufficient routine immunisation, and limited campaign scope could have contributed to this outcome. Addressing these challenges, such as diagnostics, socioeconomic support, and improved work environments are crucial for effective case management and optimal antibiotic use in low-income countries. Comprehensive approaches are needed to achieve lasting effects on antimicrobial resistance and patient care. MH-A is currently conducting research to assess the impact of vaccines in reducing antimicrobial resistance, which is funded by the Bill & Melinda Gates Foundation, and is funded by both the IDWeek (Boston, MA, USA) and World Vaccine Congress (Barcelona, Spain) for travel and accommodation to attend and present at both conferences on the role of vaccines in reducing antimicrobial resistance. TM and BVC have no competing interests to declare. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. AI-assisted technologies were used in the writing process to improve the readability and language of the work, application was done with human oversight and control and all authors carefully reviewed and edited the result. The effect of a comprehensive typhoid conjugate vaccine campaign on antimicrobial prescribing in children in Harare, Zimbabwe: a mixed methods studyNon-specific febrile illness caused by confirmed or suspected typhoid is a common cause of antimicrobial use in endemic areas. Although effective in preventing typhoid fever, we were unable to identify any effect of Typbar-TCV on antimicrobial prescribing. Ethnographic research showed the effect of contextual factors on antimicrobial prescribing, including concerns regarding safe water access, appropriate sewage disposal, health-care and diagnostic availability. To realise effects beyond disease burden reduction, holistic approaches addressing these concerns are needed so that the value of vaccines mitigating the effects of antimicrobial use as a driver of antimicrobial resistance is fully achieved. Full-Text PDF Open Access